We will conduct a Phase Ib clinical trial to determine the recommended Phase II dose (RP2D), and examine the toxicity of the niclosamide and abiraterone combination in the treatment of Castration Resistant Prostate Cancer (CRPC), and conduct pilot molecular correlative studies. Our goal is to develop a novel treatment strategy for advanced prostate cancer by targeting both full-length androgen receptor signaling as well as its variants. Abiraterone is commonly used in treating CRPC. However, the response is usually short, and resistance to abiraterone is the most common cause of treatment failure. Considerable evidence from both clinical and experimental studies demonstrated that androgen receptor variant 7 (AR-V7) plays vital roles in induction of resistance to abiraterone therapy. AR-V7 is not targeted by abiraterone. Therefore, there is urgent need to develop novel agents that target AR-V7 to overcome resistance. We discovered niclosamide as a novel inhibitor of AR-V7, and obtained extensive preclinical data showing that niclosamide synergizes abiraterone in treating CRPC. For this SBIR Phase I, we proposed to formulate niclosamide capsule under GMP procedures with the full CMC (chemistry, manufacturing and controls) information and recruit 9 patients to conduct a single-center, single-arm, open labeled trial at University of California, Davis. We will conduct pilot molecular correlated studies in these patients. Successful completion of the proposed studies will lay foundation for future phase II clinical trials, and lead to an SBIR Phase II application. This project, if successful, is high yielding and can possibly benefit hundreds of thousands of prostate cancer patients every year.